Tanox Biosystems Inc. under an SBIR Phase I grant has demonstrated the feasibility of a new dual modality immunotoxin therapeutic for AIDS. From a unique set of HIV-1 virus neutralizing monoclonal antibodies (MAbs), two antibody toxin conjugates were prepared using pokeweed antiviral protein (PAPS). The immunotoxin candidates demonstrate the same strong virus neutralizing properties as the parent antibodies and are effective in targeting and killing H9 cells (a T cell model) infected with diverse strains of the HIV-1 virus (J. Immunol. 144:1257, 1990). The Phase II application asks the question of whether the new concept of a virus neutralizing immunotoxin has the potential to succeed as an effective addition to the therapeutic arsenal against AIDS. The experiments in this proposal are designed to answer critical questions about the safety and efficacy of the most promising neutralizing immunotoxin, G3.519-PAPS and to generate supporting data for a future IND submission and proposed clinical trials.